HSV-1 is a well-characterized pathogen that encodes potent viral inhibitors that modulate both caspase activation in the apoptosis pathway and RIPK3 activation in the necroptosis pathway in a dramatic, species-specific fashion. The viral UL39-encoded viral protein ICP6, the large subunit of the virus-encoded ribonucleotide reductase, functions as a suppressor of both caspase-8 and RHIM-dependent RIPK3 activities in the natural human host. In contrast, ICP6 RHIM-mediated recruitment of RIPK3 in the nonnatural mouse host drives the direct activation of necroptosis. This chapter provides an overview of the current state of the knowledge on molecular interactions between HSV-1 viral proteins and host cell death pathways and highlights how HSV-1 manipulates cell death signals for the benefit of viral propagation.The respiratory tract is tasked with responding to a constant and vast influx of foreign agents. It acts as an important first line of defense in the innate immune system and as such plays a crucial role in preventing the entry of invading pathogens. While physical barriers like the mucociliary escalator exert their effects through the clearance of these pathogens, diverse and dynamic cellular mechanisms exist for the activation of the innate immune response through the recognition of pathogen-associated molecular patterns (PAMPs). These PAMPs are recognized by pattern recognition receptors (PRRs) that are expressed on a number of myeloid cells such as dendritic cells, macrophages, and neutrophils found in the respiratory tract. C-type lectin receptors (CLRs) are PRRs that play a pivotal role in the innate immune response and its regulation to a variety of respiratory pathogens such as viruses, bacteria, and fungi. This chapter will describe the function of both activating and inhibiting myeloid CLRs in the recognition of a number of important respiratory pathogens as well as the signaling events initiated by these receptors.C-type lectin receptors (CLRs) are a family of transmembrane proteins having at least one C-type lectin-like domain (CTLD) on the cell surface and either a short intracellular signaling tail or a transmembrane domain that facilitates interaction with a second protein, often the Fc receptor common gamma chain (FcRγ), that mediates signaling. Many CLRs directly recognize microbial cell walls and influence innate immunity by activating inflammatory and antimicrobial responses in phagocytes. In this review, we examine the contributions of certain CLRs to activation and regulation of phagocytosis in cells such as macrophages, dendritic cells and neutrophils.PURPOSE The WHO classification for IDH-mutant grade II and grade III astrocytoma may not be as prognostically meaningful as expected. We aimed to develop a novel classification system based on the DNA damage response signature. METHODS We developed the gene signature of DNA damage response with 115 samples from The Cancer Genome Atlas (TCGA) database. The dataset from Chinese Glioma Genome Atlas (CGGA) database with 41 samples was used as the validation set. Lasso Cox regression model was applied for selection of the best signature. Gene set enrichment analysis (GSEA) and gene ontology (GO) analysis were implemented to reveal its biological phenotype. RESULTS A two-gene DNA damage response signature (RAD18, MSH2) was developed using the lasso Cox regression model based on the TCGA dataset. Its prognostic efficiency was validated in the CGGA cohort. The result of Cox regression analysis showed that the signature has a better predictive accuracy than the WHO grade. The risk score was an independent prognostic factor for the overall survival of the IDH-mutant grade II and grade III astrocytoma. GSEA and GO analysis confirmed enhanced processes related to DNA damage response in high-risk group. CONCLUSION We developed a two-gene signature which can effectively predict the prognosis of patients with IDH-mutant grade II and grade III astrocytoma. It suggests a novel classification of astrocytoma with better prognostic accuracy based on the expression of DNA damage response genes.A new bilayer chiral stationary phase for use in open tubular capillary electrochromatography (OT-CEC) system is described. Gold nanoparticles were modified with L-cysteine, with a tetramethylammonium lactobionate ionic liquid that acts as the chiral selector. The gold nanoparticle-coated column provides good enantioseparation and favorable reproducibility. Compared with an uncoated separation system, the column developed displays improved separation of the racemic β-blockers propranolol, esmolol, bisoprolol and sotalol (resolutions of enotiomers are 6.29, 6.11, 6.12 and 6.02, respectively). The materials and coatings were characterized by scanning electron microscopy and transmission electron microscopy. The main driving forces (CEC and electro-osmotic flow) were studied to evaluate the variation of the immobilized columns. The effects of buffer pH value, concentration of chiral selector, type of organic modifier and applied voltage were optimized. Satisfactory relative standard deviations were achieved in run-to-run, day-to-day and column-to-column experiments. Graphical abstractSchematic preparation of a capillary column with bilayer chiral selectors coated gold nanoparticles. This novel OT-CEC system was applied for separation of four basic racemic β-blockers.In this work, novel silver sulphide quantum dots (Ag2S QD) are electrochemically quantified for the first time. The method is based on the electrochemical reduction of Ag+ to Ag0 at -0.3 V on screen-printed carbon electrodes (SPCEs), followed by anodic stripping voltammetric oxidation that gives a peak of currents at +0.06 V which represents the analytical signal. The optimized methodology allows the quantification of water-stabilized Ag2S QD in the range of approximately 2 × 109-2 × 1012 QD·mL-1 with a good reproducibility (RSD 5%). Moreover, as proof-of-concept of relevant biosensing application, Ag2S QD are evaluated as tags for Escherichia coli (E. coli) bacteria determination. Bacteria tagged with QD are separated by centrifugation from the sample solution and placed on the SPCE surface for quantitative analysis. The effect of two different Ag2S QD surface coating/stabilizing agents on both the voltammetric response and the bacteria sensing is also evaluated. 3-mercaptopropionic acid (3-MPA) is studied as model of short length coating ligand with no affinity for the bacteria, while boronic acid (BA) is evaluated as longer length ligand with chemical affinity for the polysaccharides present in the peptidoglycan layer on the bacteria cells surface. The biosensing system allows to detect bacteria in the range 10-1-103 bacteria·mL-1 with a limit of detection as low as 1 bacteria·mL-1. This methodology is a promising proof-of-concept alternative to traditional laboratory-based tests, with good sensitivity and short time and low cost of analysis. Graphical abstractNovel silver sulphide quantum dots (Ag2S QD) are electrochemically quantified for the first time. Moreover, Ag2S QD are evaluated as tags for Escherichia coli bacteria determination. The effect of two different QD surface coating ligands is also evaluated.Childhood is defined by the development of cognitive abilities as well as brain growth and function. While prior neuroimaging studies have investigated early development fragmentally, we studied the typical development of functional network connectivity continuously from infancy to childhood (average of 24 months) in 196 singleton term born children, as well as their emergence with age and visual, motor, and language abilities as assessed using the Mullen Scales of Early Learning. We demonstrate a cross-age shift to networks linked to higher-order cognitive processes, paralleling previous findings about developmental courses of functional connectivity networks. When investigating skill associations with functional connectivity independent of age, we revealed distinct network connectivity patterns for visual, motor, and language skills as each of them become more and more refined along childhood development. Specifically, the amount of functional networks recruited increases with skill complexity, with an exceeding involvement of higher order networks enabling daily maintenance and coordination of cognitive functions. Further, both motor and language network connectivity patterns overlapped in network connectivity patterns for the default mode, visual, salience, and dorsal attention networks, possibly implicating their overarching contribution to each other’s and higher cognitive development.Movement-related sensory and motor activity in the brain contributes to cognitive processes. We have observed that the frequency of stepping rhythm in head-fixed mice running on a jetball overlaps with the range of frequencies that characterize hippocampal rhythmic slow activity, including theta (~ 3 to 10 Hz). On average, step-cycle troughs (i.e. when the paw touches the ground) were weakly coupled to hippocampal theta oscillations. This weak coupling was sustained during a range of running speeds. In short temporal windows, step-cycle troughs were synchronous with hippocampal theta oscillatory cycle troughs, while during other periods they led or lagged behind theta cycles. Furthermore, simultaneously recorded theta rhythmic medial septal neurons in the basal forebrain were phase-coupled to both step-cycles and theta-cycles. We propose that the weak overall phase relationship of step-cycles with theta-cycles signifies a distinct mode of information processing. Transient synchronization of the step-cycle with theta may indicate the engagement of septo-hippocampal-entorhinal network with the current heading of the animal.OBJECTIVE Coal miners are exposed to polycyclic aromatic hydrocarbons (PAHs), a group of neurotoxicants formed and released during incomplete combustion of coal. High levels of anxiety and depression have been reported in coal miners, but little is known about neurobehavioral functions in populations that are occupationally exposed to PAHs. We tested neurobehavioral performance in coal miners and correlated it with levels of urinary markers of PAH exposure. METHODS Levels of urinary PAH metabolites were measured in 652 male coal miners as an indicator of exposure. Subjects were divided into a high-exposure group and a low-exposure group based on the median level of total PAH metabolites. A neurobehavioral core test battery and a questionnaire were used to assess neurobehavioral performance and collect demographic information, respectively. RESULTS The median level of total PAH metabolites in urine was 4.88 μmol/mol creatinine. Highly exposed workers exhibited more fatigue-inertia than less-exposed workers (p  less then  0.05), and had lower scores in forward digit span, digit symbol, and Benton visual retention tests (p  less then  0.05). Multiple linear regression indicated that age, education, and shift work were significantly correlated with test scores. CONCLUSIONS PAH exposure may be associated with neurobehavioral alterations, which should be monitored in coal miners to prevent neurobehavioral disorders.The regeneration of injured or damaged tissues by cell delivery approaches requires the fabrication of cell carriers (e.g., microspheres, MS) that allow for cell delivery to limit cells spreading from the injection site. Ideal MS for cell delivery should allow for cells adhesion and proliferation on the MS before the injection, while they should allow for viable cells release after the injection to promote the damaged tissue regeneration. We optimized a water-in-oil emulsion method to obtain gelatin MS crosslinked by methylenebisacrylamide (MBA). The method we propose allowed obtaining spherical, chemically crosslinked MS characterized by a percentage crosslinking degree of 74.5 ± 2.1%. The chemically crosslinked gelatin MS are characterized by a diameter of 70.9 ± 17.2 μm in the dry state and, at swelling plateau in culture medium at 37 °C, by a diameter of 169.3 ± 41.3 μm. The MS show dimensional stability up to 28 days, after which they undergo complete degradation. Moreover, during their degradation, MS release gelatin that can improve the engraftment of cells in the injured site.